The overall goal of this project is to further develop and evaluate a novel, non-invasive imaging and analysis method for the detection and localization of transient, repeated, but irregular changes in brain activity using functional Magnetic Resonance Imaging (fMRI). The method, 2dTCA, is based on the Temporal Clustering Analysis (TCA) of series of fMRI images and will be developed primarily to detect and localize interictal brain activity in focal epilepsy. In the proposed work, the 2dTCA image analysis algorithms and fMRI imaging protocol will first be evaluated and validated in control studies in human subjects where the timing of the stimulus is known. The validated protocol will then be performed with simultaneous electroencephalogram (EEG) recordings in two cohorts of focal epilepsy patients, (1) those with unilateral ictal discharges on scalp EEG, and (2) those with bilateral ictal discharges on scalp EEG. These data will be used to determine the relationship between the blood oxygenation responses detected and localized by fMRI and 2dTCA alone, the blood oxygenation responses identified by fMRI and simultaneous EEG, and the EEG activity at the scalp. In addition, quantitative analyses of the EEG patterns will be used to identify features of the EEG signals that may be initiating and correspond to the 2dTCA detected oxygenation response. The ultimate outcomes of the proposed study will be (1) a novel and much more clinically practical technique for detection and localization of random, transient BOLD signals that would expand analysis methods for examining interictal (between seizure) activity in epilepsy, as well as other involuntary activation models such as tics in Tourette Syndrome and hallucinations in patients with schizophrenia, and (2) a more complete understanding of the epileptic interictal activity detected by 2dTCA and its relationship to scalp EEG. This study is the foundation of a comprehensive clinical validation in the use of 2dTCA and fMRI in the identification of the seizure focus in epilepsy. If successful, the ability to utilize the spatial localization capabilities of fMRI will be available to those majority of clinical sites that cannot afford MRI-compatible EEG systems and the technical expertise required to use them, and for those patients whose lack of sufficient activity on scalp EEG prohibits the use of the simultaneous EEG methods. [unreadable] [unreadable] [unreadable]